Hemophagocytic lymphohistiocytosis after lung transplant: report of 2 cases and a literature review

Hemophagocytic lymphohistiocytosis is a rare and often fatal disease that may occur in solid organ transplant recipients. Here, we describe 2 patients who developed hemophagocytic lymphohistiocytosis after having a lung transplant and present a review of all cases of hemophagocytic lymphohistiocytosis occurring in solid organ transplant recipients. Diagnosis of hemophagocytic lymphohistiocytosis relies on the association of clinical findings and the presence of hemophagocytosis. Clinical presentation is nonspecific and patients may present with unexplained sepsis or multiple organ failure. Management consists of treating the underlying process; but unfortunately, the prognosis is poor.     

Hemophagocytic lymphohistiocytosis in adults: Diagnosis and treatment

Hemophagocytic lymphohistiocytosis occurring as a primary or acquired disorder is a condition of chaotic and uncontrolled immune system stimulation. Cytotoxic cells and macrophages cause multiorgan damage, hemophagocytosis, and severe systemic inflammation. Clinical manifestations include a fever, organ enlargement, and weight loss. Laboratory tests show bicytopenia or pancytopenia, cytolysis and cholestasis, serum ferritin elevation, and clotting disorders. The reference standard for the diagnosis remains the presence in histological specimens of hemophagocytic macrophages, which may be lacking early in the disease, leading to diagnostic challenges. Inherited forms produce symptoms in early childhood and are fatal in the absence of specific treatment. In adults, the clinical spectrum ranges from mild and self-limited hemophagocytic lymphohistiocytosis to rapidly fatal multiorgan failure. Many questions remain unresolved regarding the diagnosis and treatment in adults. This update is an attempt at providing answers.     

Nephrotic syndrome in a bone marrow transplant recipient after cyclosporine withdrawal

Sir, Chronic graft-vs-host disease (GVHD) is one of the most frequentcomplications after bone marrow transplantation. Nephrotoxicityrelated to the use of cyclosporine (CsA) is common, but nephroticsyndrome has been reported rarely. Membranous glomerulonephritishas been found in the majority of patients [1–6], andin     

Successful conversion from cyclosporine to tacrolimus for gastric motor dysfunction in a lung transplant recipient

BACKGROUND: Conversion after transplantation from cyclosporine to tacrolimus is often performed because of recurrent acute/chronic rejection or unacceptable side effects such as nephrotoxicity, arterial hypertension, and cosmetic disorders. Although gastrointestinal discomfort is often reported after transplantation, it is usually not considered a sufficient reason for conversion, although tacrolimus seems beneficial with regards to gastric motor activity in renal transplant patients. METHODS: A lung transplantation was performed in a 41-year-old woman with alpha-1 antitrypsin deficiency emphysema. Because the patient presented severe symptoms of nausea, vomiting, and dyspepsia, without obvious endoscopic explanation, that resulted in highly variable cyclosporine trough levels, she was converted from cyclosporine to tacrolimus. RESULTS: After conversion, dyspepsia, nausea, and vomiting resolved. Neurological complications caused by a transient high trough level of tacrolimus resolved completely upon dose reduction with tacrolimus trough levels remaining very stable afterwards. CONCLUSION: Tacrolimus may be the immunosuppressant of choice after solid organ transplantation in patients with problems related to gastric motor dysfunction.     

Successful outcome of a complicated pregnancy in a renal transplant recipient taking cyclosporine A

The successful outcome of a pregnancy complicated by reversible renal failure secondary to total ureteral obstruction caused by a pregnant uterus and treated temporarily with nephrostomy is reported. The cyclosporine A (CsA) and prednisone treated female recipient of a cadaveric renal allograft gave birth to a male child, which at 2080 grams was small for gestational age (35 weeks of pregnancy). The child presented neither signs of congenital anomalies or chromosome aberrations nor nephrotoxicity, hepatotoxicity or anemia. Simultaneous measurement of trough CsA blood levels (CsA RIA, Sandoz) displayed reduced values in the child's blood (mother 864 ng/ml-4 hours after oral CsA intake; son 312 ng/ml). Beside postrenal failure the patient's pregnancy was complicated by 7 rejection episodes treated with high doses of methylprednisone (total dose 5 g) with reversible damage of the transplant function, two episodes of a urinary tract infection and increasing anemia necessitating blood transfusions. The HIV negative patient had developed a Kaposi's sarcoma 6 weeks after grafting. The progression of infiltrating skin lesions during pregnancy was not seen.     

Low bioavailability of cyclosporine microemulsion and tacrolimus in a small bowel transplant recipient: possible relationship to intestinal P-glycoprotein activity

With intestine transplants the allograft is dependent on itself for maintenance of adequate immunosuppression. We evaluated an intestinal transplant recipient who required very large doses of either tacrolimus or cyclosporine emulsion to achieve acceptable blood concentrations. Pharmacokinetic studies revealed bioavailabilities of 2% and 6% respectively, while D-xylose and B12 absorption were found to be within normal limits and fecal fat was only slightly increased, suggesting that there was a selective absorptive defect for these drugs. Biopsies of the allograft ileum revealed a high P-glycoprotein activity compared to the jejunum or to intestinal biopsies from other normal subjects. This may be a contributing factor to poor immunosuppressive drug absorption in this patient and others.     

Simultaneous pancreas-kidney transplant: a single-center long-term outcome

BACKGROUND: In patients with type 1 diabetes mellitus and end-stage renal disease, simultaneous pancreas-kidney transplantation is associated with increased survival when compared with solitary deceased kidney transplant or dialysis. We consider that the analysis of our long-term program (based in a single center) of simultaneous pancreas-kidney transplantation would provide valuable information for this therapeutic approach regarding patient and organ survival. METHODS: The outcome of 57 consecutive pancreas-kidney transplants patients was analyzed. The analysis included characteristics of the donor and recipient and survival rates of patients and both grafts. We also analyzed age and modality of renal replacement treatment as possible mortality risk factors. RESULTS: Ten-year patient, kidney and pancreas graft survival rates were 75.8%, 57.2% and 42.7%, respectively. Censoring for patient death, the results for 10-year kidney and pancreas survival were 78.5% and 58%, respectively. CONCLUSION: Our results add evidence to support the notion that the double and simultaneous pancreas-kidney transplantation is in fact the treatment of choice in selected patients with end-stage renal failure due to type 1 diabetes mellitus.     

Itraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treated with simvastatin and cyclosporine

BACKGROUND: Statins are widely used to decrease cholesterol and improve morbidity and mortality associated with coronary artery disease. Myopathy constitutes a rare but potentially life-threatening adverse reaction, which is related to plasma HMG-CoA reductase inhibitory activity. Therefore, the incidence of rhabdomyolysis increases dramatically when statins are co-administered with drugs that inhibit their hepatic transformation, such as cyclosporine or azoles. METHODS AND RESULTS: We present a case of severe rhabdomyolysis and acute renal failure induced by itraconazole in a heart transplant recipient chronically treated with cyclosporine and simvastatin. The literature with regard to the pathogenetic mechanisms and the clinical implications are reviewed. CONCLUSIONS: To avoid severe myopathy, cyclosporine levels should be monitored sooner than weekly intervals and statins should be discontinued or their dosage should be reduced, as long as azoles need to be prescribed in transplant recipients. Rhabdomyolysis and acute renal insufficiency should be promptly recognized and aggressively treated.     

Successful use of cyclosporine in a lung transplant recipient with tacrolimus-associated hemolytic uremic syndrome.

Hemolytic-uremic syndrome (HUS) is a rare, but well-described complication in organ transplant recipients maintained on cyclosporine immunosuppression. Tacrolimus is a newer agent with similar immunosuppressant efficacy. In cases of cyclosporine-related HUS in renal transplant recipients, tacrolimus has been used successfully without recurrence of HUS. Tacrolimus has been reported to cause HUS in renal and more recently in cardiac transplant patients. We report a case of HUS in a lung transplant recipient receiving tacrolimus who was subsequently converted to cyclosporine without recurrence of HUS.     

Conversion from tacrolimus to cyclosporine for a non-dose-dependent tacrolimus-induced toxicity, a pediatric kidney transplant recipient case report

Tacrolimus-induced toxicity is considered a dose-related side effect largely due to a direct action of this potent calcineurin inhibitor on its targets including the kidney and the pancreas. This paper describes a case of tacrolimus systemic toxicity that appeared in a pediatric kidney transplant recipient who received a low drug dose. The kidney biopsy was a crucial aid toward the correct diagnosis, which reversed upon conversion to cyclosporine-based immunosuppression. A review of the literature suggests a chance of systemic toxicity even when the patient is maintained on therapeutic levels of tacrolimus. Because idiosyncratic reactions to the drug have not yet been postulated, we conclude that this suspicion may be addressed by a safe conversion to cyclosporine in pediatric patients.